Accutane must only be dispensed:

• in no more than a 30-day supply
• with an Accutane Medication Guide
• after authorization from the iPLEDGE program
• prior to the "do not dispense to patient after" date provided by the iPLEDGE system (within 7 days of the office visit)
• with a new prescription for refills and another authorization from the iPLEDGE program (No automatic refills are allowed)

An Accutane Medication Guide must be given to the patient each time Accutane is dispensed, as required by law. This Accutane Medication Guide is an important part of the risk management program for the patients.

Accutane must not be prescribed, dispensed or otherwise obtained through the internet or any other means outside of the iPLEDGE program. Only FDA-approved Accutane products must be distributed, prescribed, dispensed, and used. Patients must fill Accutane prescriptions only at US licensed pharmacies.

A description of the iPLEDGE program educational materials available with iPLEDGE is provided below. The main goal of these educational materials is to explain the iPLEDGE program requirements and to reinforce the educational messages.

1. The iPLEDGE Program Guide to Best Practices for Isotretinoin includes: isotretinoin teratogenic potential, information on pregnancy testing, and the method to complete a qualified isotretinoin prescription.
2. The iPLEDGE Program Prescriber Contraception Counseling Guide includes: specific information about effective contraception, the limitations of contraceptive methods, behaviors associated with an increased risk of contraceptive failure and pregnancy and the methods to evaluate pregnancy risk.
3. The iPLEDGE Program Pharmacist Guide for Isotretinoin includes: isotretinoin teratogenic potential and the method to obtain authorization to dispense an isotretinoin prescription.
4. The iPLEDGE program is a systematic approach to comprehensive patient education about their responsibilities and includes education for contraception compliance and reinforcement of educational messages. The iPLEDGE program includes information on the risks and benefits of isotretinoin which is linked to the Medication Guide dispensed by pharmacists with each isotretinoin prescription.
5. Female patients not of childbearing potential and male patients, and female patients of childbearing potential are provided with separate booklets. Each booklet contains information on isotretinoin therapy including precautions and warnings, a Patient Information/Informed Consent (for all patients) form, and a toll-free line which provides isotretinoin information in 2 languages.
6. The booklet for female patients not of childbearing potential and male patients, The iPLEDGE Program Guide to Isotretinoin for Male Patients and Female Patients Who Cannot Get Pregnant , also includes information about male reproduction and a warning not to share isotretinoin with others or to donate blood during isotretinoin therapy and for 1 month following discontinuation of isotretinoin.
7. The booklet for female patients of childbearing potential, The iPLEDGE Program Guide to Isotretinoin for Female Patients Who Can Get Pregnant , includes a referral program that offers female patients free contraception counseling, reimbursed by the manufacturer, by a reproductive specialist; and a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form concerning birth defects.
8. The booklet, The iPLEDGE Program Birth Control Workbook includes information on the types of contraceptive methods, the selection and use of appropriate, effective contraception, the rates of possible contraceptive failure and a toll-free contraception counseling line.
9. In addition, there is a patient educational DVD with the following videos -- "Be Prepared, Be Protected" and "Be Aware: The Risk of Pregnancy While on Isotretinoin" (see Information for Patients ).

General

Although an effect of Accutane on bone loss is not established, physicians should use caution when prescribing Accutane to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsant.

Patients may be at increased risk when participating in sports with repetitive impact where the risks of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known. There are spontaneous reports of fractures and/or delayed healing in patients while on therapy with Accutane or following cessation of therapy with Accutane while involved in these activities. While causality to Accutane has not been established, an effect must not be ruled out.

Information for Patients

See PRECAUTIONS and Boxed CONTRAINDICATIONS AND WARNINGS .

• Patients must be instructed to read the Medication Guide supplied as required by law when Accutane is dispensed. The complete text of the Medication Guide is reprinted at the end of this document. For additional information, patients must also be instructed to read the iPLEDGE program patient educational materials. All patients must sign the Patient Information/Informed Consent (for all patients) form.
• Female patients of childbearing potential must be instructed that they must not be pregnant when Accutane therapy is initiated, and that they should use 2 forms of effective contraception simultaneously for 1 month before starting Accutane, while taking Accutane, and for 1 month after Accutane has been stopped, unless they commit to continuous abstinence from heterosexual intercourse. They should also sign a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form prior to beginning Accutane therapy. They should be given an opportunity to view the patient DVD provided by the manufacturer to the prescriber. The DVD includes information about contraception, the most common reasons that contraception fails, and the importance of using 2 forms of effective contraception when taking teratogenic drugs and comprehensive information about types of potential birth defects which could occur if a female patient who is pregnant takes Accutane at any time during pregnancy. Female patients should be seen by their prescribers monthly and have a urine or serum pregnancy test, in a CLIA-certified laboratory, performed each month during treatment to confirm negative pregnancy status before another Accutane prescription is written (see Boxed CONTRAINDICATIONS AND WARNINGS and PRECAUTIONS ).
• Accutane is found in the semen of male patients taking Accutane, but the amount delivered to a female partner would be about 1 million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin induced embryopathy is unknown, 20 years of postmarketing reports include 4 with isolated defects compatible with features of retinoid exposed fetuses; however 2 of these reports were incomplete, and 2 had other possible explanations for the defects observed.
• Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of Accutane treatment, patients and family members should be asked about any history of psychiatric disorder, and at each visit during treatment patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses, and persistent physical symptoms unresponsive to treatment. Patients should stop Accutane and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of Accutane treatment may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient's family. A referral to a mental health professional may be necessary. The physician should consider whether Accutane therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Accutane therapy.
• Patients must be informed that some patients, while taking Accutane or soon after stopping Accutane, have become depressed or developed other serious mental problems. Symptoms of depression include sad, "anxious" or empty mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating. Some patients taking Accutane have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives. There were reports that some of these people did not appear depressed. There have been reports of patients on Accutane becoming aggressive or violent. No one knows if Accutane caused these behaviors or if they would have happened even if the person did not take Accutane. Some people have had other signs of depression while taking Accutane.
• Patients must be informed that they must not share Accutane with anyone else because of the risk of birth defects and other serious adverse events.
• Patients must be informed not to donate blood during therapy and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to Accutane.
• Patients should be reminded to take Accutane with a meal (see DOSAGE AND ADMINISTRATION ). To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid.
• Patients should be informed that transient exacerbation (flare) of acne has been seen, generally during the initial period of therapy.
• Wax epilation and skin resurfacing procedures (such as dermabrasion, laser) should be avoided during Accutane therapy and for at least 6 months thereafter due to the possibility of scarring (see ADVERSE REACTIONS : Skin and Appendages ).
• Patients should be advised to avoid prolonged exposure to UV rays or sunlight.
• Patients should be informed that they may experience decreased tolerance to contact lenses during and after therapy.
• Patients should be informed that approximately 16% of patients treated with Accutane in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug. Transient pain in the chest has been reported less frequently. In the clinical trial, these symptoms generally cleared rapidly after discontinuation of Accutane, but in some cases persisted (see ADVERSE REACTIONS : Musculoskeletal ). There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity (see Laboratory Tests: CPK ).
• Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with Accutane developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of Accutane. Consideration should be given to discontinuation of Accutane if any significant abnormality is found.
• Neutropenia and rare cases of agranulocytosis have been reported. Accutane should be discontinued if clinically significant decreases in white cell counts occur.

Hypersensitivity

Anaphylactic reactions and other allergic reactions have been reported. Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement (including renal) have been reported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical management.

Drug Interactions

• Vitamin A:    Because of the relationship of Accutane to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects.
• Tetracyclines:    Concomitant treatment with Accutane and tetracyclines should be avoided because Accutane use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines.
• Micro-dosed Progesterone Preparations:    Micro-dosed progesterone preparations ("minipills" that do not contain an estrogen) may be an inadequate method of contraception during Accutane therapy. Although other hormonal contraceptives are highly effective, there have been reports of pregnancy from female patients who have used combined oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products. These reports are more frequent for female patients who use only a single method of contraception. It is not known if hormonal contraceptives differ in their effectiveness when used with Accutane. Therefore, it is critically important for female patients of childbearing potential to select and commit to use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form (see PRECAUTIONS ).
• Norethindrone/ethinyl estradiol:    In a study of 31 premenopausal female patients with severe recalcitrant nodular acne receiving OrthoNovum® 7/7/7 Tablets as an oral contraceptive agent, Accutane at the recommended dose of 1 mg/kg/day, did not induce clinically relevant changes in the pharmacokinetics of ethinyl estradiol and norethindrone and in the serum levels of progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prescribers are advised to consult the package insert of medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products.
• St. John's Wort:    Accutane use is associated with depression in some patients (see WARNINGS : Psychiatric Disorders and ADVERSE REACTIONS : Psychiatric ). Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort.
• Phenytoin:    Accutane has not been shown to alter the pharmacokinetics of phenytoin in a study in seven healthy volunteers. These results are consistent with the in vitro finding that neither isotretinoin nor its metabolites induce or inhibit the activity of the CYP 2C9 human hepatic P450 enzyme. Phenytoin is known to cause osteomalacia. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between phenytoin and Accutane. Therefore, caution should be exercised when using these drugs together.
• Systemic Corticosteroids:    Systemic corticosteroids are known to cause osteoporosis. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between systemic corticosteroids and Accutane. Therefore, caution should be exercised when using these drugs together.

Laboratory Tests

• Pregnancy Test:
  
  • Female patients of childbearing potential must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Accutane prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for Accutane. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests must be at least 19 days.
  • For patients with regular menstrual cycles, the second pregnancy test must be done during the first 5 days of the menstrual period and within 7 days following the office visit, immediately preceding the beginning of Accutane therapy and after the patient has used 2 forms of contraception for 1 month.
  • For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, the second pregnancy test must be done within 7 days following the office visit, immediately preceding the beginning of Accutane therapy and after the patient has used 2 forms of contraception for 1 month.
  • Each month of therapy, patients must have a negative result from a urine or serum pregnancy test. A pregnancy test must be repeated each month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription.
• Lipids:    Pretreatment and follow-up blood lipids should be obtained under fasting conditions. After consumption of alcohol, at least 36 hours should elapse before these determinations are made. It is recommended that these tests be performed at weekly or biweekly intervals until the lipid response to Accutane is established. The incidence of hypertriglyceridemia is 1 patient in 4 on Accutane therapy (see WARNINGS : Lipids ).
• Liver Function Tests:    Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to Accutane has been established (see WARNINGS : Hepatotoxicity ).
• Glucose:    Some patients receiving Accutane have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during Accutane therapy, although no causal relationship has been established.
• CPK:    Some patients undergoing vigorous physical activity while on Accutane therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. In a clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, transient elevations in CPK were observed in 12% of patients, including those undergoing strenuous physical activity in association with reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these patients, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal within 4 weeks. No cases of rhabdomyolysis were reported in this trial.

Carcinogenesis, Mutagenesis and Impairment of Fertility

In male and female Fischer 344 rats given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 to 5.3 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to the human population is uncertain.

The Ames test was conducted with isotretinoin in two laboratories. The results of the tests in one laboratory were negative while in the second laboratory a weakly positive response (less than 1.6 × background) was noted in S. typhimurium TA100 when the assay was conducted with metabolic activation. No dose-response effect was seen and all other strains were negative. Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse micronucleus test, S. cerevisiae D7 assay, in vitro clastogenesis assay with human-derived lymphocytes, and unscheduled DNA synthesis assay) were all negative.

In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of isotretinoin of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area).

In dogs, testicular atrophy was noted after treatment with oral isotretinoin for approximately 30 weeks at dosages of 20 or 60 mg/kg/day (10 or 30 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of spermatogenesis but some sperm were observed in all testes examined and in no instance were completely atrophic tubules seen. In studies of 66 men, 30 of whom were patients with nodular acne under treatment with oral isotretinoin, no significant changes were noted in the count or motility of spermatozoa in the ejaculate. In a study of 50 men (ages 17 to 32 years) receiving Accutane (isotretinoin) therapy for nodular acne, no significant effects were seen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose.

Pregnancy: Category X. See Boxed CONTRAINDICATIONS AND WARNINGS .

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because of the potential for adverse effects, nursing mothers should not receive Accutane.

Pediatric Use

The use of Accutane in pediatric patients less than 12 years of age has not been studied. The use of Accutane for the treatment of severe recalcitrant nodular acne in pediatric patients ages 12 to 17 years should be given careful consideration, especially for those patients where a known metabolic or structural bone disease exists (see PRECAUTIONS : General ). Use of Accutane in this age group for severe recalcitrant nodular acne is supported by evidence from a clinical study comparing 103 pediatric patients (13 to 17 years) to 197 adult patients (>/=18 years). Results from this study demonstrated that Accutane, at a dose of 1 mg/kg/day given in two divided doses, was equally effective in treating severe recalcitrant nodular acne in both pediatric and adult patients.

In studies with Accutane, adverse reactions reported in pediatric patients were similar to those described in adults except for the increased incidence of back pain and arthralgia (both of which were sometimes severe) and myalgia in pediatric patients (see ADVERSE REACTIONS ).

In an open-label clinical trial (N=217) of a single course of therapy with Accutane for severe recalcitrant nodular acne, bone density measurements at several skeletal sites were not significantly decreased (lumbar spine change >-4% and total hip change >-5%) or were increased in the majority of patients. One patient had a decrease in lumbar spine bone mineral density >4% based on unadjusted data. Sixteen (7.9%) patients had decreases in lumbar spine bone mineral density >4%, and all the other patients (92%) did not have significant decreases or had increases (adjusted for body mass index). Nine patients (4.5%) had a decrease in total hip bone mineral density >5% based on unadjusted data. Twenty-one (10.6%) patients had decreases in total hip bone mineral density >5%, and all the other patients (89%) did not have significant decreases or had increases (adjusted for body mass index). Follow-up studies performed in 8 of the patients with decreased bone mineral density for up to 11 months thereafter demonstrated increasing bone density in 5 patients at the lumbar spine, while the other 3 patients had lumbar spine bone density measurements below baseline values. Total hip bone mineral densities remained below baseline (range -1.6% to -7.6%) in 5 of 8 patients (62.5%).

In a separate open-label extension study of 10 patients, ages 13 to 18 years, who started a second course of Accutane 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25% (see WARNINGS : Skeletal : Bone Mineral Density ).

Geriatric Use

Clinical studies of isotretinoin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with isotretinoin therapy (see WARNINGS and PRECAUTIONS ).

ADVERSE REACTIONS

Clinical Trials and Postmarketing Surveillance

The adverse reactions listed below reflect the experience from investigational studies of Accutane, and the postmarketing experience. The relationship of some of these events to Accutane therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, eg, of the lips, nasal passage, and eyes).

Dose Relationship

Cheilitis and hypertriglyceridemia are usually dose related. Most adverse reactions reported in clinical trials were reversible when therapy was discontinued; however, some persisted after cessation of therapy (see WARNINGS and ADVERSE REACTIONS ).

Body as a Whole

allergic reactions, including vasculitis, systemic hypersensitivity (see PRECAUTIONS : Hypersensitivity ), edema, fatigue, lymphadenopathy, weight loss

Cardiovascular

palpitation, tachycardia, vascular thrombotic disease, stroke

Endocrine/Metabolic

hypertriglyceridemia (see WARNINGS : Lipids ), alterations in blood sugar levels (see PRECAUTIONS : Laboratory Tests )

Gastrointestinal

inflammatory bowel disease (see WARNINGS : Inflammatory Bowel Disease ), hepatitis (see WARNINGS : Hepatotoxicity ), pancreatitis (see WARNINGS : Lipids ), bleeding and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, nausea, other nonspecific gastrointestinal symptoms

Hematologic

allergic reactions (see PRECAUTIONS : Hypersensitivity ), anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PRECAUTIONS : Information for Patients ). See PRECAUTIONS : Laboratory Tests for other hematological parameters.

Musculoskeletal

skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density (see WARNINGS : Skeletal ), musculoskeletal symptoms (sometimes severe) including back pain, myalgia, and arthralgia (see PRECAUTIONS : Information for Patients ), transient pain in the chest (see PRECAUTIONS : Information for Patients ), arthritis, tendonitis, other types of bone abnormalities, elevations of CPK/rare reports of rhabdomyolysis (see PRECAUTIONS : Laboratory Tests ).

Neurological

pseudotumor cerebri (see WARNINGS : Pseudotumor Cerebri ), dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke, syncope, weakness

Psychiatric

suicidal ideation, suicide attempts, suicide, depression, psychosis, aggression, violent behaviors (see WARNINGS : Psychiatric Disorders ), emotional instability

Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy.

Reproductive System

abnormal menses

Respiratory

bronchospasms (with or without a history of asthma), respiratory infection, voice alteration

Skin and Appendages

acne fulminans, alopecia (which in some cases persists), bruising, cheilitis (dry lips), dry mouth, dry nose, dry skin, epistaxis, eruptive xanthomas, ⁷ flushing, fragility of skin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, infections (including disseminated herpes simplex), nail dystrophy, paronychia, peeling of palms and soles, photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial erythema, seborrhea, and eczema), sunburn susceptibility increased, sweating, urticaria, vasculitis (including Wegener's granulomatosis; see PRECAUTIONS : Hypersensitivity ), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see PRECAUTIONS : Information for Patients )

Special Senses

Hearing

hearing impairment (see WARNINGS : Hearing Impairment ), tinnitus.

Vision

corneal opacities (see WARNINGS : Corneal Opacities ), decreased night vision which may persist (see WARNINGS : Decreased Night Vision ), cataracts, color vision disorder, conjunctivitis, dry eyes, eyelid inflammation, keratitis, optic neuritis, photophobia, visual disturbances

Urinary System

glomerulonephritis (see PRECAUTIONS : Hypersensitivity ), nonspecific urogenital findings (see PRECAUTIONS : Laboratory Tests for other urological parameters)

Laboratory

Elevation of plasma triglycerides (see WARNINGS : Lipids ), decrease in serum high-density lipoprotein (HDL) levels, elevations of serum cholesterol during treatment

Increased alkaline phosphatase, SGOT (AST), SGPT (ALT), GGTP or LDH (see WARNINGS : Hepatotoxicity )

Elevation of fasting blood sugar, elevations of CPK (see PRECAUTIONS : Laboratory Tests ), hyperuricemia

Decreases in red blood cell parameters, decreases in white blood cell counts (including severe neutropenia and rare reports of agranulocytosis; see PRECAUTIONS : Information for Patients ), elevated sedimentation rates, elevated platelet counts, thrombocytopenia

White cells in the urine, proteinuria, microscopic or gross hematuria

OVERDOSAGE

The oral LD ₅₀ of isotretinoin is greater than 4000 mg/kg in rats and mice (>600 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the rat dose for total body surface area and >300 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1.0 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolve without apparent residual effects.

Accutane causes serious birth defects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS ). Female patients of childbearing potential who present with isotretinoin overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the Boxed CONTRAINDICATIONS AND WARNINGS . Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in PRECAUTIONS . Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a female patient who is or might become pregnant, for 1 month after the overdose. All patients with isotretinoin overdose should not donate blood for at least 1 month.

DOSAGE AND ADMINISTRATION

Accutane should be administered with a meal (see PRECAUTIONS : Information for Patients ).

The recommended dosage range for Accutane is 0.5 to 1.0 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1.0 mg/kg/day, ⁸ it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects -- some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2.0 mg/kg/day, as tolerated. Failure to take Accutane with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions.

The safety of once daily dosing with Accutane has not been established. Once daily dosing is not recommended.

If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Accutane, even in low doses, has not been studied, and is not recommended. It is important that Accutane be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Accutane on bone loss is unknown (see WARNINGS : Skeletal : Bone Mineral Density , Hyperostosis , and Premature Epiphyseal Closure ).

Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS ).

HOW SUPPLIED

Soft gelatin capsules, 10 mg (light pink), imprinted ACCUTANE 10 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0155-49).

Soft gelatin capsules, 20 mg (maroon), imprinted ACCUTANE 20 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0169-49).

Soft gelatin capsules, 40 mg (yellow), imprinted ACCUTANE 40 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0156-49).

Storage

Store at controlled room temperature (59° to 86°F, 15° to 30°C). Protect from light.

PRODUCT PHOTO(S):

REFERENCES

1. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acne with 13- cis -retinoic acid. N Engl J Med 300:329-333, 1979.
2. Pochi PE, Shalita AR, Strauss JS, Webster SB. Report of the consensus conference on acne classification. J Am Acad Dermatol 24:495-500, 1991.
3. Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13- cis -retinoic acid: evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol 3:602-611, 1980.
4. Jones H, Blanc D, Cunliffe WJ. 13- cis -retinoic acid and acne. Lancet 2:1048-1049, 1980.
5. Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980.
6. Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ. Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10:1024-1029, 1984.
7. Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13- cis -retinoic acid). Arch Dermatol 116:951-952, 1980.
8. Strauss JS, Rapini RP, Shalita AR, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10:490-496, 1984.

OrthoNovum 7/7/7 is a registered trademark of Ortho-McNeil Pharmaceutical, Inc.

Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant)

To be completed by the patient (and her parent or guardian* if patient is under age 18) and signed by her doctor.

Read each item below and initial in the space provided to show that you understand each item and agree to follow your doctor's instructions. Do not sign this consent and do not take isotretinoin if there is anything that you do not understand.

*A parent or guardian of a minor patient (under age 18) must also read and initial each item before signing the consent.

______________________________________________________

(Patient's Name)

1. I understand that there is a very high chance that my unborn baby could have severe birth defects if I am pregnant or become pregnant while taking isotretinoin. This can happen with any amount and even if taken for short periods of time. This is why I must not be pregnant while taking isotretinoin.
   Initial: ______
2. I understand that I must not get pregnant 1 month before, during the entire time of my treatment, and for 1 month after the end of my treatment with isotretinoin.
   Initial: ______
3. I understand that I must avoid sexual intercourse completely, or I must use 2 separate, effective forms of birth control (contraception) at the same time . The only exceptions are if I have had surgery to remove the uterus (a hysterectomy) or both of my ovaries (bilateral oophorectomy), or my doctor has medically confirmed that I am post-menopausal.
   Initial: ______
4. I understand that hormonal birth control products are among the most effective forms of birth control. Combination birth control pills and other hormonal products include skin patches, shots, under-the-skin implants, vaginal rings, and intrauterine devices (IUDs). Any form of birth control can fail. That is why I must use 2 different birth control methods at the same time, starting 1 month before, during, and for 1 month after stopping therapy every time I have sexual intercourse, even if 1 of the methods I choose is hormonal birth control.
   Initial: ______
5. I understand that the following are effective forms of birth control:
   

   Primary forms Secondary forms · tying my tubes (tubal sterilization) Barrier forms (always used with spermicide): · partner's vasectomy · male latex condom · intrauterine device · diaphragm · hormonal (combination birth control pills, skin patches, shots, under-the- skin implants, or vaginal ring) · cervical cap Others: · vaginal sponge (contains spermicide)

   
   A diaphragm, condom, and cervical cap must each be used with spermicide, a special cream that kills sperm
   I understand that at least 1 of my 2 forms of birth control must be a primary method.
   Initial: ______
6. I will talk with my doctor about any medicines including herbal products I plan to take during my isotretinoin treatment because hormonal birth control methods may not work if I am taking certain medicines or herbal products.
   Initial: ______
7. I may receive a free birth control counseling session from a doctor or other family planning expert. My isotretinoin doctor can give me an isotretinoin Patient Referral Form for this free consultation.
   Initial: ______
8. I must begin using the birth control methods I have chosen as described above at least 1 month before I start taking isotretinoin.
   Initial: ______
9. I cannot get my first prescription for isotretinoin unless my doctor has told me that I have 2 negative pregnancy test results. The first pregnancy test should be done when my doctor decides to prescribe isotretinoin. The second pregnancy test must be done in a lab during the first 5 days of my menstrual period right before starting isotretinoin therapy treatment, or as instructed by my doctor. I will then have 1 pregnancy test; in a lab.
   
   • every month during treatment
   • at the end of treatment
   • and 1 month after stopping treatment
     I must not start taking isotretinoin until I am sure that I am not pregnant, have negative results from 2 pregnancy tests, and the second test has been done in a lab.
     Initial: ______
10. I have read and understand the materials my doctor has given to me, including The iPLEDGE Program Guide for Isotretinoin for Female Patients Who Can Get Pregnant, The iPLEDGE Birth Control Workbook and The iPLEDGE Program Patient Introductory Brochure.
    My doctor gave me and asked me to watch the DVD containing a video about birth control and a video about birth defects and isotretinoin.
    I was told about a private counseling line that I may call for more information about birth control. I have received information on emergency birth control.
    Initial: ______
11. I must stop taking isotretinoin right away and call my doctor if I get pregnant, miss my expected menstrual period, stop using birth control, or have sexual intercourse without using my 2 birth control methods at any time.
    Initial: ______
12. My doctor gave me information about the purpose and importance of providing information to the iPLEDGE program should I become pregnant while taking isotretinoin or within 1 month of the last dose. If I become pregnant, I agree to be contacted by the iPLEDGE program and be asked questions about my pregnancy. I also understand that if I become pregnant, information about my pregnancy, my health, and my baby's health may be given to the maker of isotretinoin and government health regulatory authorities.
    Initial: ______
13. I understand that being qualified to receive isotretinoin in the iPLEDGE program means that I:
    
    • have had 2 negative urine or blood pregnancy tests before receiving the first isotretinoin prescription. The second test must be done in a lab. I must have a negative result from a urine or blood pregnancy test done in a lab repeated each month before I receive another isotretinoin prescription.
    • have chosen and agreed to use 2 forms of effective birth control at the same time. At least 1 method must be a primary form of birth control, unless I have chosen never to have sexual contact with a male (abstinence) , or I have undergone a hysterectomy. I must use 2 forms of birth control for at least 1 month before I start isotretinoin therapy, during therapy, and for 1 month after stopping therapy. I must receive counseling, repeated on a monthly basis, about birth control and behaviors associated with an increased risk of pregnancy.
    • have signed a Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) that contains warnings about the chance of possible birth defects if I am pregnant or become pregnant and my unborn baby is exposed to isotretinoin.
    • have been informed of and understand the purpose and importance of providing information to the iPLEDGE program should I become pregnant while taking isotretinoin or within 1 month of the last dose. I agree to be contacted by the iPLEDGE program and be asked questions about my pregnancy.
    • have interacted with the iPLEDGE program before starting isotretinoin and on a monthly basis to answer questions on the program requirements and to enter my two chosen forms of birth control.
      Initial: ______

My doctor has answered all my questions about isotretinoin and I understand that it is my responsibility not to get pregnant 1 month before, during isotretinoin treatment , or for 1 month after I stop taking isotretinoin .

Initial: ______

I now authorize my doctor ________________ to begin my treatment with isotretinoin.

Patient Signature:_______________________Date:__________

Parent/Guardian Signature (if under age 18): _____________________________Date: ____________________

Please print: Patient Name and Address__________________

__________________________Telephone ___________________

I have fully explained to the patient, __________________, the nature and purpose of the treatment described above and the risks to females of childbearing potential. I have asked the patient if she has any questions regarding her treatment with isotretinoin and have answered those questions to the best of my ability.

Doctor Signature: ________________________Date:_________

PLACE THE ORIGINAL SIGNED DOCUMENTS IN THE PATIENT'S MEDICAL RECORD. PLEASE PROVIDE A COPY TO THE PATIENT.

Patient Information/Informed Consent (for all patients):

To be completed by patient (parent or guardian if patient is under age 18) and signed by the doctor.

Read each item below and initial in the space provided if you understand each item and agree to follow your doctor's instructions. A parent or guardian of a patient under age 18 must also read and understand each item before signing the agreement.

Do not sign this agreement and do not take isotretinoin if there is anything that you do not understand about all the information you have received about using isotretinoin.

1. I, _________________________________________________,
   (Patient's Name)
   understand that isotretinoin is a medicine used to treat severe nodular acne that cannot be cleared up by any other acne treatments, including antibiotics. In severe nodular acne, many red, swollen, tender lumps form in the skin. If untreated, severe nodular acne can lead to permanent scars.
   Initials: ______
2. My doctor has told me about my choices for treating my acne.
   Initials: ______
3. I understand that there are serious side effects that may happen while I am taking isotretinoin. These have been explained to me. These side effects include serious birth defects in babies of pregnant patients. [Note: There is a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant)].
   Initials: ______
4. I understand that some patients, while taking isotretinoin or soon after stopping isotretinoin, have become depressed or developed other serious mental problems. Symptoms of depression include sad, "anxious" or empty mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating. Some patients taking isotretinoin have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives. There were reports that some of these people did not appear depressed. There have been reports of patients on isotretinoin becoming aggressive or violent. No one knows if isotretinoin caused these behaviors or if they would have happened even if the person did not take isotretinoin. Some people have had other signs of depression while taking isotretinoin (see #7 below).
   Initials: ______
5. Before I start taking isotretinoin, I agree to tell my doctor if I have ever had symptoms of depression (see #7 below), been psychotic, attempted suicide, had any other mental problems, or take medicine for any of these problems. Being psychotic means having a loss of contact with reality, such as hearing voices or seeing things that are not there.
   Initials: ______
6. Before I start taking isotretinoin, I agree to tell my doctor if, to the best of my knowledge, anyone in my family has ever had symptoms of depression, been psychotic, attempted suicide, or had any other serious mental problems.
   Initials: ______
7. Once I start taking isotretinoin, I agree to stop using isotretinoin and tell my doctor right away if any of the following signs and symptoms of depression or psychosis happen. I:
   
   • Start to feel sad or have crying spells
   • Lose interest in activities I once enjoyed
   • Sleep too much or have trouble sleeping
   • Become more irritable, angry, or aggressive than usual (for example, temper outbursts, thoughts of violence)
   • Have a change in my appetite or body weight
   • Have trouble concentrating
   • Withdraw from my friends or family
   • Feel like I have no energy
   • Have feelings of worthlessness or guilt
   • Start having thoughts about hurting myself or taking my own life (suicidal thoughts)
   • Start acting on dangerous impulses
   • Start seeing or hearing things that are not real
   
   Initials: ______
8. I agree to return to see my doctor every month I take isotretinoin to get a new prescription for isotretinoin, to check my progress, and to check for signs of side effects.
   Initials: ______
9. Isotretinoin will be prescribed just for me -- I will not share isotretinoin with other people because it may cause serious side effects, including birth defects.
   Initials: ______
10. I will not give blood while taking isotretinoin or for 1 month after I stop taking isotretinoin. I understand that if someone who is pregnant gets my donated blood, her baby may be exposed to isotretinoin and may be born with serious birth defects.
    Initials: ______
11. I have read the The iPLEDGE Program Patient Introductory Brochure , and other materials my provider gave me containing important safety information about isotretinoin. I understand all the information I received.
    Initials: ______
12. My doctor and I have decided I should take isotretinoin. I understand that I must be qualified in the iPLEDGE program to have my prescription filled each month. I understand that I can stop taking isotretinoin at any time. I agree to tell my doctor if I stop taking isotretinoin.
    Initials: ______

I now allow my doctor ___________________________ to begin my treatment with isotretinoin.

Patient Signature: ______________________Date: __________

Parent/Guardian Signature (if under age 18): __________________________________Date: _______________

Patient Name (print) ___________________________________

Patient Address __________________ Telephone (___.___.___)

________________________________________________

I have:

• fully explained to the patient, __________________, the nature and purpose of isotretinoin treatment, including its benefits and risks
• given the patient the appropriate educational materials, The iPLEDGE Program Patient Introductory Brochure and asked the patient if he/she has any questions regarding his/her treatment with isotretinoin
• answered those questions to the best of my ability

Doctor Signature: ________________________Date:_________

PLACE THE ORIGINAL SIGNED DOCUMENTS IN THE PATIENT'S MEDICAL RECORD. PLEASE PROVIDE A COPY TO THE PATIENT.

MEDICATION GUIDE

ACCUTANE (ACK-u-tane)

(isotretinoin capsules)

Read the Medication Guide that comes with Accutane before you start taking it and each time you get a prescription. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about Accutane?

• Accutane is used to treat a type of severe acne (nodular acne) that has not been helped by other treatments, including antibiotics.
• Because Accutane can cause birth defects, Accutane is only for patients who can understand and agree to carry out all of the instructions in the iPLEDGE program.
• Accutane may cause serious mental health problems.

1. Birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby, and early (premature) births. Female patients who are pregnant or who plan to become pregnant must not take Accutane. Female patients must not get pregnant:
   
   • for 1 month before starting Accutane
   • while taking Accutane
   • for 1 month after stopping Accutane.
   
   If you get pregnant while taking Accutane, stop taking it right away and call your doctor. Doctors and patients should report all cases of pregnancy to:
   
   • FDA MedWatch at 1-800-FDA-1088, and
   • the iPLEDGE pregnancy registry at 1-866-495-0654
2. Serious mental health problems. Accutane may cause:
   
   • depression
   • psychosis (seeing or hearing things that are not real)
   • suicide. Some patients taking Accutane have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives.

Stop Accutane and call your doctor right away if you or a family member notices that you have any of the following signs and symptoms of depression or psychosis:

• start to feel sad or have crying spells
• lose interest in activities you once enjoyed
• sleep too much or have trouble sleeping
• become more irritable, angry, or aggressive than usual (for example, temper outbursts, thoughts of violence)
• have a change in your appetite or body weight
• have trouble concentrating
• withdraw from your friends or family
• feel like you have no energy
• have feelings of worthlessness or guilt
• start having thoughts about hurting yourself or taking your own life (suicidal thoughts)
• start acting on dangerous impulses
• start seeing or hearing things that are not real

After stopping Accutane, you may also need follow-up mental health care if you had any of these symptoms.

What is Accutane?

Accutane is a medicine taken by mouth to treat the most severe form of acne (nodular acne) that cannot be cleared up by any other acne treatments, including antibiotics. Accutane can cause serious side effects (see "What is the most important information I should know about Accutane?" ). Accutane can only be:

• prescribed by doctors that are registered in the iPLEDGE program
• dispensed by a pharmacy that is registered with the iPLEDGE program
• given to patients who are registered in the iPLEDGE program and agree to do everything required in the program

What is severe nodular acne?

Severe nodular acne is when many red, swollen, tender lumps form in the skin. These can be the size of pencil erasers or larger. If untreated, nodular acne can lead to permanent scars.

Who should not take Accutane?

• Do not take Accutane if you are pregnant, plan to become pregnant, or become pregnant during Accutane treatment. Accutane causes severe birth defects. See "What is the most important information I should know about Accutane?"
• Do not take Accutane if you are allergic to anything in it. Accutane contains parabens as the preservative. See the end of this Medication Guide for a complete list of ingredients in Accutane.

What should I tell my doctor before taking Accutane?

Tell your doctor if you or a family member has any of the following health conditions:

• mental problems
• asthma
• liver disease
• diabetes
• heart disease
• bone loss (osteoporosis) or weak bones
• an eating problem called anorexia nervosa (where people eat too little)
• food or medicine allergies

Tell your doctor if you are pregnant or breastfeeding. Accutane must not be used by women who are pregnant or breastfeeding.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Accutane and certain other medicines can interact with each other, sometimes causing serious side effects. Especially tell your doctor if you take:

• Vitamin A supplements. Vitamin A in high doses has many of the same side effects as Accutane. Taking both together may increase your chance of getting side effects.
• Tetracycline antibiotics. Tetracycline antibiotics taken with Accutane can increase the chances of getting increased pressure in the brain.
• Progestin-only birth control pills (mini-pills). They may not work while you take Accutane. Ask your doctor or pharmacist if you are not sure what type you are using.
• Dilantin (phenytoin). This medicine taken with Accutane may weaken your bones.
• Corticosteroid medicines. These medicines taken with Accutane may weaken your bones.
• St. John's Wort. This herbal supplement may make birth control pills work less effectively.

These medicines should not be used with Accutane unless your doctor tells you it is okay.

Know the medicines you take. Keep a list of them to show to your doctor and pharmacist. Do not take any new medicine without talking with your doctor.

How should I take Accutane?

• You must take Accutane exactly as prescribed. You must also follow all the instructions of the iPLEDGE program. Before prescribing Accutane, your doctor will:
  
  • explain the iPLEDGE program to you
  • have you sign the Patient Information/Informed Consent (for all patients). Female patients who can get pregnant must also sign another consent form.
    You will not be prescribed Accutane if you cannot agree to or follow all the instructions of the iPLEDGE program.
• You will get no more than a 30-day supply of Accutane at a time. This is to make sure you are following the Accutane iPLEDGE program. You should talk with your doctor each month about side effects.
• The amount of Accutane you take has been specially chosen for you. It is based on your body weight, and may change during treatment.
• Take Accutane 2 times a day with a meal, unless your doctor tells you otherwise. Swallow your Accutane capsules whole with a full glass of liquid. Do not chew or suck on the capsule. Accutane can hurt the tube that connects your mouth to your stomach (esophagus) if it is not swallowed whole.
• If you miss a dose, just skip that dose. Do not take 2 doses at the same time.
• If you take too much Accutane or overdose, call your doctor or poison control center right away.
• Your acne may get worse when you first start taking Accutane. This should last only a short while. Talk with your doctor if this is a problem for you.
• You must return to your doctor as directed to make sure you don't have signs of serious side effects. Your doctor may do blood tests to check for serious side effects from Accutane. Female patients who can get pregnant will get a pregnancy test each month.
• Female patients who can get pregnant must agree to use 2 separate forms of effective birth control at the same time 1 month before, while taking, and for 1 month after taking Accutane. You must access the iPLEDGE system to answer questions about the program requirements and to enter your 2 chosen forms of birth control. To access the iPLEDGE system, go to www.ipledgeprogram.com or call 1-866-495-0654.
  You must talk about effective birth control methods with your doctor or go for a free visit to talk about birth control with another doctor or family planning expert. Your doctor can arrange this free visit, which will be paid for by the company that makes Accutane.
  If you have sex at any time without using 2 forms of effective birth control, get pregnant, or miss your expected period, stop using Accutane and call your doctor right away.

What should I avoid while taking Accutane?

• Do not get pregnant while taking Accutane and for 1 month after stopping Accutane. See "What is the most important information I should know about Accutane?"
• Do not breast feed while taking Accutane and for 1 month after stopping Accutane. We do not know if Accutane can pass through your milk and harm the baby.
• Do not give blood while you take Accutane and for 1 month after stopping Accutane. If someone who is pregnant gets your donated blood, her baby may be exposed to Accutane and may be born with birth defects.
• Do not take other medicines or herbal products with Accutane unless you talk to your doctor. See "What should I tell my doctor before taking Accutane?"
• Do not drive at night until you know if Accutane has affected your vision. Accutane may decrease your ability to see in the dark.
• Do not have cosmetic procedures to smooth your skin, including waxing, dermabrasion, or laser procedures, while you are using Accutane and for at least 6 months after you stop. Accutane can increase your chance of scarring from these procedures. Check with your doctor for advice about when you can have cosmetic procedures.
• Avoid sunlight and ultraviolet lights as much as possible. Tanning machines use ultraviolet lights. Accutane may make your skin more sensitive to light.
• Do not share Accutane with other people. It can cause birth defects and other serious health problems.

What are the possible side effects of Accutane?

• Accutane can cause birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby, and early (premature) births. See "What is the most important information I should know about Accutane?"
• Accutane may cause serious mental health problems. See "What is the most important information I should know about Accutane?"
• serious brain problems. Accutane can increase the pressure in your brain. This can lead to permanent loss of eyesight and, in rare cases, death. Stop taking Accutane and call your doctor right away if you get any of these signs of increased brain pressure:
  
  • bad headache
  • blurred vision
  • dizziness
  • nausea or vomiting
  • seizures (convulsions)
  • stroke
• stomach area (abdomen) problems. Certain symptoms may mean that your internal organs are being damaged. These organs include the liver, pancreas, bowel (intestines), and esophagus (connection between mouth and stomach). If your organs are damaged, they may not get better even after you stop taking Accutane. Stop taking Accutane and call your doctor if you get:
  
  • severe stomach, chest or bowel pain
  • trouble swallowing or painful swallowing
  • new or worsening heartburn
  • diarrhea
  • rectal bleeding
  • yellowing of your skin or eyes
  • dark urine
• bone and muscle problems. Accutane may affect bones, muscles, and ligaments and cause pain in your joints or muscles. Tell your doctor if you plan hard physical activity during treatment with Accutane. Tell your doctor if you get:
  
  • back pain
  • joint pain
  • broken bone. Tell all healthcare providers that you take Accutane if you break a bone.
  
  Stop Accutane and call your doctor right away if you have muscle weakness. Muscle weakness with or without pain can be a sign of serious muscle damage.
  Accutane may stop long bone growth in teenagers who are still growing.
• hearing problems. Stop using Accutane and call your doctor if your hearing gets worse or if you have ringing in your ears. Your hearing loss may be permanent.
• vision problems. Accutane may affect your ability to see in the dark. This condition usually clears up after you stop taking Accutane, but it may be permanent. Other serious eye effects can occur. Stop taking Accutane and call your doctor right away if you have any problems with your vision or dryness of the eyes that is painful or constant. If you wear contact lenses, you may have trouble wearing them while taking Accutane and after treatment.
• lipid (fats and cholesterol in blood) problems. Accutane can raise the level of fats and cholesterol in your blood. This can be a serious problem. Return to your doctor for blood tests to check your lipids and to get any needed treatment. These problems usually go away when Accutane treatment is finished.
• serious allergic reactions. Stop taking Accutane and get emergency care right away if you develop hives, a swollen face or mouth, or have trouble breathing. Stop taking Accutane and call your doctor if you get a fever, rash, or red patches or bruises on your legs.
• blood sugar problems. Accutane may cause blood sugar problems including diabetes. Tell your doctor if you are very thirsty or urinate a lot.
• decreased red and white blood cells. Call your doctor if you have trouble breathing, faint, or feel weak.
• The common, less serious side effects of Accutane are dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds. Call your doctor if you get any side effect that bothers you or that does not go away.

These are not all of the possible side effects with Accutane. Your doctor or pharmacist can give you more detailed information.

How should I store Accutane?

• Store Accutane at room temperature, between 59° and 86°F. Protect from light.
• Keep Accutane and all medicines out of the reach of children.

General Information about Accutane

Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use Accutane for a condition for which it was not prescribed. Do not give Accutane to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Accutane. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Accutane that is written for health care professionals. You can also call iPLEDGE program at 1-866-495-0654 or visit www.ipledgeprogram.com .

What are the ingredients in Accutane?

Active Ingredient:   Isotretinoin

Inactive Ingredients:   beeswax, butylated hydroxyanisole, edetate disodium, hydrogenated soybean oil flakes, hydrogenated vegetable oil, and soybean oil. Gelatin capsules contain glycerin and parabens (methyl and propyl), with the following dye systems: 10 mg -- iron oxide (red) and titanium dioxide; 20 mg -- FD&C Red No. 3, FD&C Blue No. 1, and titanium dioxide; 40 mg -- FD&C Yellow No. 6, D&C Yellow No. 10, and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Dilantin is a registered trademark of Warner-Lambert Company LLC.

Revised: August 2005